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Osteoarthritis (OA) is a common joint disorder affecting about 7% of the global population, primarily characterized by the gradual loss of articular cartilage. This degeneration results from local inflammation, matrix depletion, and direct cartilage damage. A critical element in this process is the activation of the stimulator of the interferon genes (STING) pathway. Emerging evidence highlights its potential as a therapeutic target, with natural products showing promise as inhibitors. Our study centers on Acacetin, a basic unit of polyketides known for its anti-inflammatory properties. Prior research has highlighted its potential interaction with STING based on the structure. Thus, this study aimed to assess the effectiveness of Acacetin as a STING inhibitor and its protective role against OA. In vitro experiments showed that Acacetin pretreatment not only mitigated interleukin-1ß (IL-1ß)-induced cytotoxicity but also decreased the inflammatory response and degeneration in chondrocytes stimulated IL-1ß. In vivo studies revealed that Acacetin administration significantly reduced articular cartilage destruction, abnormal bone remodeling, and osteophyte formation in a model of OA induced by destabilization of the medial meniscus (DMM). Mechanistically, Acacetin was found to interact directly with STING, and inhibit IL-1ß-induced activation of STING, along with the subsequent phosphorylation of the TBK1/NF-κB pathway in chondrocytes. In conclusion, our findings establish Acacetin as an effective inhibitor of STING that protects chondrocytes from IL-1ß-induced damage and slows the progression of OA in mice.
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OBJECTIVE: The study aims to determine the effects of Nd:YAG laser-assisted with subgingival scaling and root planing (SRP) treatment on glucose control and the dynamic changes of subgingival microbiome in periodontitis with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Twenty-two patients were split into Nd:YAG group (n = 11) and SRP group (n = 11). Patients in the Nd:YAG group received SRP and auxiliary Nd:YAG laser treatment; patients in the SRP group received SRP treatment only. Periodontal tissue inflammation and glycemic control were assessed and analyzed during the treatment period and the changes of subgingival microbiome were analyzed by full-length 16S rRNA sequencing. RESULTS: After 3 months of treatment, PD and CAL values improved significantly in the Nd:YAG group compared to the SRP group. BOP in both groups improved significantly after treatment. FPG levels in the Nd:YAG group were significantly reduced after treatment. Porphyromonas and Porphyromonadaceae were enriched in the Nd:YAG group at baseline, and Fusobacteriota, Fusobacteriia, Fusobacteriales, Leptotrichiaceae, and Leptotrichia were enriched after treatment. CONCLUSION: Nd:YAG laser-assisted SRP therapy has additional benefits in improving periodontal tissue inflammation and blood glucose control in periodontitis patients with T2DM compared with SRP therapy alone and there was a trend towards a decrease in disease-associated taxa and an increase in health-associated taxa following auxiliary Nd:YAG laser treatment. CLINICAL RELEVANCE: The effects of Nd:YAG laser-assisted SRP treatment on inflammation, glucose control, and subgingival microbiome in periodontitis patients with T2DM were elucidated, and new ideas for the treatment of T2DM periodontitis were provided.
Asunto(s)
Diabetes Mellitus Tipo 2 , Terapia por Láser , Láseres de Estado Sólido , Periodontitis , Humanos , Animales , Aplanamiento de la Raíz , Glucemia , Diabetes Mellitus Tipo 2/complicaciones , ARN Ribosómico 16S , Raspado Dental , Periodontitis/complicaciones , Periodontitis/terapia , InflamaciónRESUMEN
BACKGROUND: The BCL-2 family is crucial for cell death regulation and is involved in development, tissue homeostasis, and immunity. This study aimed to investigate the association between genetic variants in BCL-2 family genes and non-syndromic cleft lip with or without cleft palate (NSCL/P) risk. METHODS: A two-stage case-control study was conducted in this association study. Gene-based analysis using Multi-marker Analysis of GenoMic Annotation was performed in the first stage cohort, which included 565 cases and 1269 controls. A logistic regression model was employed to assess the effect of single nucleotide polymorphisms (SNPs) on susceptibility to NSCL/P. Candidate SNPs were replicated by extra dbGaP case-parent trios. Haploreg, RegulomeDB, and UCSC Genome Browser were used to identify enhancer effects of promising SNPs. Bulk RNA sequencing data obtained from the Gene Expression Omnibus was used to identify co-expressed genes. Single-cell RNA sequencing dataset was used to infer the cell population of the candidate gene. The "Monocle" package was used to analyze the pseudotime cell trajectories. RESULTS: Rs3943258 located in the enhancer region was associated with the risk of NSCL/P (Pmeta = 5.66 × 10-04 ) and exhibited an eQTL effect for BCL2 (P = 3.96 × 10-02 ). Co-expression and pathway enrichment analysis revealed that genes related to Bcl2 were significantly enriched in the PI3K-Akt signaling pathway, MAPK signaling pathway, and Wnt signaling pathway. Five cell clusters were identified in single-cell RNA sequencing, and Bcl2 was mainly located in the mesenchyme. CONCLUSION: The rs3943258 located within BCL2 was probably related to NSCL/P susceptibility.